We are conducting studies to elucidate the cause and pathogenesis of chronic degenerative disorders of the CNS particular emphasis on MS, ALS, Parkinsonism, Pick's and Alzheimer's diseases, Huntington's chorea and other presenile dementias. We have proved that chronic degenerative disease of man, even familial, apparently genetically determined disorders, may be slow virus infections with incubation periods of decades; and have defined a group of subacute spongiform virus encephalopathies, including kuru and Creutzfeldt-Jakob disease(CJD) of man, scrapie of sheep, and mink encephalopathy, all caused by slow, very unconventional, viruses. The unusual properties of these unique viruses pose important theoretical problems for the whole of medicine, microbiology and molecular biology, and the elucidation of their physical and chemical properties and the mechanisms of replication, therefore, forms the current focus of endeavor. These studies have led to a definition of transmissible virus dementias as an increasingly recognized cause of death throughout the world, and the recent discovery of high incidence foci of such disease in Israel and elsewhere and the probable transmission of such infection by corneal transplantation and as an occupational hazard, as from exposure to human brain in surgery and pathology. Transmission to primates of scrapie from American sheep, with a disease indistinguishable from experimental CJD, further emphasizes the possible relationship of this widespread disease of sheep to human neuropathology. In the quest for in vitro propagation of the viruses of these diseases in tissue culture systems, many strains of oncornaviruses, herpesviruses and papovaviruses, adenoviruses and myxoviruses have been isolated and defined. The presence of such agents in the brains of healthy monkeys and apes, some of which are reverse transcriptase producing oncornaviruses, and many of which are highly oncogenic, has linked these studies closely with cancer research, enhancing the link already established by the demonstration of slowly developing noninflammatory pathogenic effects from persistent, masked and defective infection. Zonal UC, electrophoretic, chromatographic purification; UV ionizing radiation inactivation; EM freeze fracture membrane studies on scrapie are under way.